Beat-to-beat variability is an independent and early indicator for d-sotalol-induced arrhythmias in vivo

Abstract

Background: Beat-to-beat variability of repolarization (BVR) has been associated with sudden cardiac death in patients and with drug-induced proarrhythmia in isolated rabbit hearts. This study tried to relate repolarization parameters, including BVR. to drug induced torsades de pointes (TdP) arrhythmias in dogs. Methods: 2 and 4 “g/kg d-Sotalol (dS) were administered in a random crossover design to 8 anesthetized dogs with chronic AV block. Endocardial MAP durations (MAPD) from both ventricles (LV and RV) and surface EGG were recorded; Interventricular dispersion (LV - RV MAPD) and extrasystolic (ES) frequency were calculated. BVR was quantified by the area of the Pomcar~ plots (figure) for LV, RV MAPD and QT during 30.beat periods at baseline (BL) and in the presence of dS just prior to extrasystolic activity preceding TdP. Results: The repolarization parameters (QT, LV, RV MAPD and dispersion) could not account for the difference in TdP occurrence (218 vs. 618 after 2 and 4 mglkg dS, respectively). In contrast, the LV Potncare plot area and the frequency of multiple extrasystoles .(mES) were higher in the 4 mglkg group. BVR was present before ES occurred and independent of the other repolarization parameters. Conclusions: Where the QT-duration and the other repolarization parameters failed, beat-to-beat variability of the LV and the frequency of “ES corresponded with the dosedependent TdP induction. BVR is an Independent and early measurement that could become important in predicting drug-induced TdP.